Mitochondrial quality control via organelle and protein degradation.

ABSTRACT

Mitochondria are essential eukaryotic organelles that produce ATP as well as synthesize various macromolecules. They also participate in signalling pathways such as the innate immune response and apoptosis. These diverse functions are performed by >1,000 different mitochondrial proteins. Although mitochondria are continuously exposed to potentially damaging conditions such as reactive oxygen species, proteases/peptidases localized in different mitochondrial subcompartments, termed mitoproteases, maintain mitochondrial quality and integrity. In addition to processing incoming precursors and degrading damaged proteins, mitoproteases also regulate metabolic reactions, mitochondrial protein half-lives and gene transcription. Impaired mitoprotease function is associated with various pathologies. In this review, we highlight recent advances in our understanding of mitochondrial quality control regulated by autophagy, ubiquitin-proteasomes and mitoproteases.